Mulugeta Russom1, Yodit Fitsum2, Abiel Abraham3, Ruth L Savage4,5,6. 1. Eritrean Pharmacovigilance Centre, National Medicines and Food Administration, Ministry of Health, Asmara, Eritrea. satiswt@gmail.com. 2. Eritrean Pharmacovigilance Centre, National Medicines and Food Administration, Ministry of Health, Asmara, Eritrea. 3. Akordat Hospital, Ministry of Health, Akordat, Eritrea. 4. Uppsala Monitoring Centre, Uppsala, Sweden. 5. Division of Health Sciences, New Zealand Pharmacovigilance Centre, University of Otago, Dunedin, New Zealand. 6. Department of General Practice, University of Otago, Christchurch, New Zealand.
Abstract
BACKGROUND: Diclofenac, a nonsteroidal anti-inflammatory drug, is not a documented cause of rhabdomyolysis in the Summaries of Product Characteristics held by major regulators. There are, however, eight published single case reports that associate rhabdomyolysis with diclofenac. OBJECTIVE: Triggered by a serious local case report, this study was conducted to evaluate the evidence for a causal association between diclofenac and rhabdomyolysis. PATIENTS AND METHODS: A descriptive analysis of rhabdomyolysis associated with diclofenac was conducted by mining data from the WHO Global Database of Individual Case Safety Reports, VigiBase, and published case reports. RESULTS: 70 eligible cases were retrieved from VigiBase. The median age was 56.5 years (range 1-90). Where reported precisely (26 reports), the median time to onset of rhabdomyolysis following administration of diclofenac was 3 days. In 20 cases, diclofenac was reported as a sole suspect and was solely administered in 14 of these. In 30 cases, rhabdomyolysis abated following withdrawal of diclofenac. Seven of these cases fulfilled the WHO-UMC case-causality assessment criteria for 'probable'. Diclofenac was probably an indirect cause in another five reports where rhabdomyolysis ensued from injection-site necrosis. There were eight fatalities and intramuscular administration was over-represented in this group. In 27 patients taking lipid-lowering agents, the incidence of acute kidney injury with rhabdomyolysis was 62.9% compared with 37.1% for the whole cohort. Off-label use of diclofenac for minor or undiagnosed conditions was reported. CONCLUSION: Currently available data suggests a causal link between diclofenac and rhabdomyolysis either directly or indirectly.
BACKGROUND:Diclofenac, a nonsteroidal anti-inflammatory drug, is not a documented cause of rhabdomyolysis in the Summaries of Product Characteristics held by major regulators. There are, however, eight published single case reports that associate rhabdomyolysis with diclofenac. OBJECTIVE: Triggered by a serious local case report, this study was conducted to evaluate the evidence for a causal association between diclofenac and rhabdomyolysis. PATIENTS AND METHODS: A descriptive analysis of rhabdomyolysis associated with diclofenac was conducted by mining data from the WHO Global Database of Individual Case Safety Reports, VigiBase, and published case reports. RESULTS: 70 eligible cases were retrieved from VigiBase. The median age was 56.5 years (range 1-90). Where reported precisely (26 reports), the median time to onset of rhabdomyolysis following administration of diclofenac was 3 days. In 20 cases, diclofenac was reported as a sole suspect and was solely administered in 14 of these. In 30 cases, rhabdomyolysis abated following withdrawal of diclofenac. Seven of these cases fulfilled the WHO-UMC case-causality assessment criteria for 'probable'. Diclofenac was probably an indirect cause in another five reports where rhabdomyolysis ensued from injection-site necrosis. There were eight fatalities and intramuscular administration was over-represented in this group. In 27 patients taking lipid-lowering agents, the incidence of acute kidney injury with rhabdomyolysis was 62.9% compared with 37.1% for the whole cohort. Off-label use of diclofenac for minor or undiagnosed conditions was reported. CONCLUSION: Currently available data suggests a causal link between diclofenac and rhabdomyolysis either directly or indirectly.
Authors: Rafael Siqueira Athayde Lima; Geraldo Bezerra da Silva Junior; Alexandre Braga Liborio; Elizabeth De Francesco Daher Journal: Saudi J Kidney Dis Transpl Date: 2008-09